Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors

Publication date: Available online 15 June 2017
Source:Cancer Cell
Author(s): Kun Qu, Lisa C. Zaba, Ansuman T. Satpathy, Paul G. Giresi, Rui Li, Yonghao Jin, Randall Armstrong, Chen Jin, Nathalie Schmitt, Ziba Rahbar, Hideki Ueno, William J. Greenleaf, Youn H. Kim, Howard Y. Chang
Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4⁺ T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4⁺ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

Graphical abstract

Teaser

Qu et al. show that the accessible chromatin landscape distinguishes leukemic from host T cells in cutaneous T cell lymphoma (CTCL) patients as well as T cells from healthy individuals. The clinical response of CTCL to HDAC inhibitors strongly associates with a concurrent gain in chromatin accessibility.


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